A Study of Tirzepatide (LY3298176) Versus Placebo in Participants With Type 2 Diabetes Inadequately Controlled on Insulin Glargine With or Without Metformin (SURPASS-5)
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| ClinicalTrials.gov Identifier: NCT04039503 |
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Recruitment Status :
Completed
First Posted : July 31, 2019
Results First Posted : January 12, 2022
Last Update Posted : January 12, 2022
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Sponsor:
Eli Lilly and Company
Information provided by (Responsible Party):
Eli Lilly and Company
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Brief Summary:
The purpose of this study is to compare the safety and efficacy of the study drug tirzepatide to placebo in participants with type 2 diabetes that are already on insulin glargine, with or without metformin. Participants will administer tirzepatide or placebo along with their previous glucose lowering medications. The study will last approximately 47 weeks and may include about 23 visits.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Type 2 Diabetes | Drug: Tirzepatide Drug: Placebo | Phase 3 |
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 475 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Double (Participant, Investigator) |
| Primary Purpose: | Treatment |
| Official Title: | Randomized, Phase 3, Double-blind Trial Comparing the Effect of the Addition of Tirzepatide Versus Placebo in Patients With Type 2 Diabetes Inadequately Controlled on Insulin Glargine With or Without Metformin |
| Actual Study Start Date : | August 30, 2019 |
| Actual Primary Completion Date : | December 22, 2020 |
| Actual Study Completion Date : | January 13, 2021 |
Resource links provided by the National Library of Medicine
MedlinePlus Genetics related topics:
Type 2 diabetes
Drug Information available for:
Tirzepatide
| Arm | Intervention/treatment |
|---|---|
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Experimental: 5 mg Tirzepatide
5 milligrams (mg) tirzepatide administered subcutaneously (SC) once a week.
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Drug: Tirzepatide
Administered SC as add-on to the pre-trial background medication.
Other Name: LY3298176 |
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Experimental: 10 mg Tirzepatide
10 mg tirzepatide administered SC once a week.
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Drug: Tirzepatide
Administered SC as add-on to the pre-trial background medication.
Other Name: LY3298176 |
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Experimental: 15 mg Tirzepatide
15 mg tirzepatide administered SC once a week.
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Drug: Tirzepatide
Administered SC as add-on to the pre-trial background medication.
Other Name: LY3298176 |
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Placebo Comparator: Placebo
Placebo administered SC once a week.
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Drug: Placebo
Administered SC as add-on to the pre-trial background medication. |
Primary Outcome Measures :
- Change From Baseline in Hemoglobin A1c (HbA1c) (10 mg and 15 mg) [ Time Frame: Baseline, Week 40 ]HbA1c is the glycosylated fraction of hemoglobin A. HbA1c is measured primarily to identify average plasma glucose concentration over prolonged periods of time. Least Squares (LS) mean was determined by mixed-model repeated measures (MMRM) model with Baseline + Baseline Metformin Use (Yes, No) + Pooled Country + Treatment + Time + Treatment*Time (Type III sum of squares).
Secondary Outcome Measures :
- Change From Baseline in HbA1c (5 mg) [ Time Frame: Baseline, Week 40 ]HbA1c is the glycosylated fraction of hemoglobin A. HbA1c is measured primarily to identify average plasma glucose concentration over prolonged periods of time. Least Squares (LS) mean was determined by mixed-model repeated measures (MMRM) model with Baseline + Baseline Metformin Use (Yes, No) + Pooled Country + Treatment + Time + Treatment*Time (Type III sum of squares).
- Change From Baseline in Body Weight [ Time Frame: Baseline, Week 40 ]Least Squares (LS) mean was determined by mixed-model repeated measures (MMRM) model with Baseline + Baseline HbA1c Group (<= 8.0%, >8.0%) + Baseline Metformin Use (Yes, No) + Pooled Country + Treatment + Time + Treatment*Time (Type III sum of squares).
- Percentage of Participants Achieving an HbA1c Target Value of <7% [ Time Frame: Week 40 ]Hemoglobin A1c (HbA1c) is the glycosylated fraction of hemoglobin A.HbA1c is measured to identify average plasma glucose concentration over prolonged periods of time.
- Change From Baseline in Fasting Serum Glucose [ Time Frame: Baseline, Week 40 ]Fasting serum glucose (FSG) is a test to determine sugar levels in serum sample after an overnight fast. LS Mean was determined by MMRM model with Baseline + Pooled Country + Baseline Metformin Use (Yes, No) + Baseline HbA1c Group (<= 8.0%, >8.0%) + Treatment + Time + Treatment*Time (Type III sum of squares) as variables.
- Mean Change From Baseline in Daily Average 7-Point Self-Monitored Blood Glucose (SMBG) Values [ Time Frame: Baseline, Week 40 ]The self-monitored plasma glucose (SMBG) data were collected at the following 7 time points: Morning Premeal - Fasting, Morning 2-hour Postmeal, Midday Premeal, Midday 2-hour Postmeal, Evening Premeal, Evening 2-hour Postmeal and Bedtime. Least Squares (LS) mean was determined by mixed-model repeated measures (MMRM) model with Baseline + Baseline HbA1c Group (<= 8.0%, >8.0%) + Baseline Metformin Use (Yes, No) + Pooled Country + Treatment (Type III sum of squares).
- Percentage of Participants Who Achieved Weight Loss ≥5% [ Time Frame: Week 40 ]Percentage of Participants who Achieved Weight Loss ≥5%.
- Percentage Change From Baseline in Daily Mean Insulin Glargine Dose [ Time Frame: Baseline, Week 40 ]LS mean was calculated using MMRM model with log (Baseline) + Baseline Metformin Use (Yes, No) + Pooled Country + Baseline HbA1c Group (<= 8.0%, >8.0%) + Treatment + Time + Treatment*Time (Type III sum of squares) as variables.
- Rate of Hypoglycemia With Blood Glucose <54 Milligram/Deciliter (mg/dL) [<3.0 Millimole/Liter (mmol/L)] or Severe Hypoglycemia [ Time Frame: Baseline through Safety Follow-Up (Up to Week 44) ]The hypoglycemia events were defined by participant reported events with blood glucose <54mg/dL) (<3.0 mmol/L] or severe hypoglycemia. Severe hypoglycemia is defined as an episode with severe cognitive impairment requiring the assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions. These episodes may be associated with sufficient neuroglycopenia to induce seizure or coma. The rate of postbaseline hypoglycemia was estimated by negative binomial model: number of episodes = Pooled Country + Baseline Metformin Use (Yes, No) + Baseline HbA1c Group (<= 8.0%, >8.0%) + Treatment, with log (exposure in days/365.25) as an offset variable.
- Pharmacokinetics (PK): Steady State Area Under the Concentration Time Curve (AUC) of Tirzepatide [ Time Frame: Week 7, 15, 23 and 39 post dose ]AUC is a combined measure obtained from Week 7, 15, 23 and 39 and a single averaged measure of AUC was reported.
- Percentage of Participants Achieving an HbA1c Target Value of <5.7% [ Time Frame: Week 40 ]Hemoglobin A1c (HbA1c) is the glycosylated fraction of hemoglobin A. HbA1c is measured to identify average plasma glucose concentration over prolonged periods of time.
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
- Have been diagnosed with type 2 diabetes mellitus (T2DM) and have been treated with insulin glargine (U100), once daily with or without metformin ≥3 months prior to screening visit.
- Have HbA1c between ≥7.0% and ≤10.5%.
- Have a stable weight (± 5%) for at least 3 months before screening.
- Have a body mass index (BMI) ≥23 kilograms per meter squared (kg/m²) at screening.
Exclusion Criteria:
- Have type 1 diabetes mellitus.
- Have had chronic or acute pancreatitis any time prior to study entry.
- Have proliferative diabetic retinopathy or diabetic maculopathy or nonproliferative diabetic retinopathy requiring acute treatment.
- Have disorders associated with slowed emptying of the stomach, or have had any stomach surgeries for the purpose of weight loss.
- Have an estimated glomerular filtration rate <30 mL/minute/1.73 m² [for participants on metformin, estimated glomerular filtration rate <45 mL/min/1.73 m2 (or lower than the country-specific threshold for using the protocol-required dose of metformin per local label)]
- Have had a heart attack, stroke, or hospitalization for congestive heart failure in the past 2 months.
- Have a personal or family history of medullary thyroid carcinoma or personal history of multiple endocrine neoplasia syndrome type 2.
- Have been taking weight loss drugs, including over-the-counter medications during the last 3 months.
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04039503
Locations
Show 48 study locations
Sponsors and Collaborators
Eli Lilly and Company
Investigators
| Study Director: | Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST) | Eli Lilly and Company |
Study Documents (Full-Text)
Documents provided by Eli Lilly and Company:
Documents provided by Eli Lilly and Company:
Study Protocol [PDF] June 26, 2020
Statistical Analysis Plan [PDF] February 1, 2021
Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | Eli Lilly and Company |
| ClinicalTrials.gov Identifier: | NCT04039503 |
| Other Study ID Numbers: |
16998 I8F-MC-GPGI ( Other Identifier: Eli Lilly and Company ) 2019-000860-99 ( EudraCT Number ) |
| First Posted: | July 31, 2019 Key Record Dates |
| Results First Posted: | January 12, 2022 |
| Last Update Posted: | January 12, 2022 |
| Last Verified: | December 1, 2021 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | Yes |
| Plan Description: | Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement. |
| Supporting Materials: |
Study Protocol Statistical Analysis Plan (SAP) Clinical Study Report (CSR) |
| Time Frame: | Data are available 6 months after the primary publication and approval of the indication studied in the US and EU, whichever is later. Data will be indefinitely available for requesting. |
| Access Criteria: | A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement. |
| URL: | http://vivli.org/ |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Keywords provided by Eli Lilly and Company:
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glucose-dependent insulinotropic polypeptide (GIP) glucagon-like peptide-1 (GLP-1) GIP/GLP-1 dual receptor agonist T2DM |
Additional relevant MeSH terms:
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Tirzepatide Diabetes Mellitus Diabetes Mellitus, Type 2 Glucose Metabolism Disorders Metabolic Diseases Endocrine System Diseases |
Hypoglycemic Agents Physiological Effects of Drugs Incretins Hormones Hormones, Hormone Substitutes, and Hormone Antagonists |